Idiopathic retroperitoneal fibrosis: an update for nephrologists

Our plain-English summary of Idiopathic retroperitoneal fibrosis: an update for nephrologists, by V. Raglianti, G.M. Rossi, A. Vaglio (Nephrology, Dialysis, Transplantation, 2021).

The study

• Authors: V. Raglianti, G.M. Rossi, A. Vaglio
• Journal: Nephrology, Dialysis, Transplantation
• Published: 2021;36(10):1773-1781
• Type of article: Review
• Cited by: 49 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Idiopathic retroperitoneal fibrosis (IRF) is a rare condition characterized by the development of a peri-aortic and peri-iliac tissue showing chronic inflammatory infiltrates and pronounced fibrosis. Ureteral entrapment with consequent obstructive uropathy is one of the most common complications of IRF, which can lead to acute renal failure and, in the long term, to varying degrees of chronic kidney disease. IRF may be isolated or develop in association with autoimmune diseases (e.g. Hashimoto's thyroiditis and psoriasis) and other fibro-inflammatory disorders (often within the spectrum of immunoglobulin G4-related disease), which suggests that it should be considered as a potentially systemic condition. IRF is an immune-mediated disease: genetic variants (e.g. human leukocyte antigen (HLA)-DRB1*03) and environmental agents (mainly exposure to asbestos and smoking) are strongly associated with an increased risk of developing the disease, while a complex network of chemokines (e.g. CXCL12 and C-C moti chemokine 11 (CCL11)) and cytokines [e.g. interleukin (IL)-6, IL-12 and IL-13] is likely to orchestrate the inflammatory response and simultaneously promote fibrosis. Glucocorticoids, alone or in combination with traditional immunosuppressants such as methotrexate and mycophenolate mofetil, are usually efficacious and promptly induce disease remission; however, up to 50% of patients relapse, thus requiring repeat immunosuppressive courses. Biologic drugs, namely rituximab, are being explored for the treatment of IRF. In addition to medical therapies, interventional procedures (mainly ureteral stenting) are required to relieve ureteral obstruction, whereas surgical ureterolysis is generally reserved to refractory cases. If appropriately treated, then the overall and renal prognosis of IRF are good, with <5% patients developing end-stage renal disease.

© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

In plain English

This narrative review, for kidney specialists, covered idiopathic retroperitoneal fibrosis (IRF), a rare disease in which fibro-inflammatory tissue surrounds the abdominal aorta and iliac arteries and can trap the ureters. It reported no new patient data. It cited a Finnish study (Uibu et al.) reporting an association between occupational asbestos exposure and increased IRF risk; the mechanism remained unclear. In a case-control study by the authors' group, asbestos exposure had an odds ratio of 4.91 (95% CI 0.78–28.02, a range including values below 1). Smoking for more than 5 years had an odds ratio of 3.15 (95% CI 1.4–11.11). Combined tobacco and asbestos exposure had odds ratios of 13.50 (95% CI 4.40–51.40) with occupational and 8.42 (95% CI 2.77–30.58) with extra-occupational asbestos exposure. No fiber type was named. A cited trial enrolled patients already in remission after one month of prednisone. By 8 months, 6% of those continuing prednisone and 39% of those switched to tamoxifen had relapsed. The authors concluded that adequately treated IRF usually has a good kidney prognosis, that end-stage kidney disease is rare, and that IRF should be managed as a potentially systemic condition.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of the literature on idiopathic retroperitoneal fibrosis, covering epidemiology, risk factors, pathology, clinical features, diagnosis, treatment and outcome. It includes a table compiling published patient series. No new patient data were collected.
• Who was studied: Published studies on idiopathic retroperitoneal fibrosis. Table 1 compiled seven patient series (21 to 204 patients each) from Italy, China, India, Tunisia, Germany and the USA. They were identified in English-language PubMed literature from 2009–19; only studies with outcome data and more than 20 patients were selected.
• Exposure: Asbestos exposure, occupational and extra-occupational, with no fiber type specified. Tobacco smoking was considered alone and combined with asbestos. Drugs, cancers, infections, radiotherapy and surgery were discussed as causes of secondary (non-idiopathic) retroperitoneal fibrosis.
• Main results:
  • Cited study (Uibu et al., Finland): reported an association between occupational asbestos exposure and increased risk of IRF. Those authors did not investigate the mechanism, but suggested the lymphatic system may carry asbestos bodies from the lungs to the retroperitoneum.
  • Cited findings: in patients with a known history of asbestos exposure, asbestos bodies have been found in various organs, including retroperitoneal organs such as the kidney and adrenal glands.
  • Cited case-control study by the authors' group: exposure to cigarette smoke for more than 5 years was associated with an odds ratio of developing IRF of 3.15 (95% CI 1.4–11.11).
  • Same cited study: asbestos exposure was associated with an odds ratio of 4.91 (95% CI 0.78–28.02).
  • Same cited study: combined exposure to tobacco and asbestos was reported to have a multiplicative effect on risk. The odds ratio was 13.50 (95% CI 4.40–51.40) after stratification for occupational exposure and 8.42 (95% CI 2.77–30.58) for extra-occupational exposure.
  • Cited open-label randomized trial of prednisone versus tamoxifen for maintaining remission. Patients had first achieved remission with one month of prednisone 1 mg/kg daily, then either continued prednisone or switched to tamoxifen. By the end of 8 months, 6% in the prednisone arm and 39% in the tamoxifen arm had relapsed.
  • Across published series, end-stage renal disease in IRF occurred with a frequency below 5% in most series.
• The authors' conclusion: The authors concluded that, if adequately treated with interventional procedures and medical therapy, renal prognosis in IRF is usually good and end-stage renal disease is rare. Because IRF is not uncommonly associated with other autoimmune or fibro-inflammatory disorders, they concluded it should be managed as a potentially systemic condition.
• Limitations the authors state:
  • The mechanism by which asbestos exposure might lead to IRF was not investigated in the cited study and remains unclear.
  • Strong evidence from controlled trials is lacking for tamoxifen and for other immunosuppressive and biological drugs.
  • Prognostic factors and predictors of recurrence have not been clearly identified, partly because management and monitoring of IRF are not standardized.
  • Further studies are needed to understand the disease's causes and define optimal treatment.

Topics

Medical terms in this study, explained in our Lexicon: Idiopathic, Fibrosis, Cytokine, Prognosis.

Related studies

• Asbestos and idiopathic retroperitoneal fibrosis — J.C. Boulard, T. Hanslik, et al. (1995)
• Asbestos and smoking as risk factors for idiopathic retroperitoneal fibrosis: a case-control study — M. Goldoni, S. Bonini, et al. (2014)
• Idiopathic retroperitoneal fibrosis: prospective evaluation of incidence and clinicoradiologic presentation — E.F.H. van Bommel, I. Jansen, et al. (2009)
• Retroperitoneal fibrosis: new insights into clinical presentation and diagnosis — A. Vaglio (2009)
• Asbestos exposure as a risk factor for retroperitoneal fibrosis — T. Uibu, P. Oksa, et al. (2004)
• Asbestos exposure: a potential cause of retroperitoneal fibrosis — R. Sauni, P. Oksa, et al. (1998)

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